{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:15:44Z","timestamp":1778786144013,"version":"3.51.4"},"reference-count":30,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Poor postoperative outcomes have been reported after surgery for infective endocarditis (IE). Whether the absence of positive cultures impacts the prognosis remains a matter of discussion. The aim of this study was to evaluate the impact of negative cultures on the prognosis of surgically treated IE.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a single-center, retrospective study. From January 2000 to June 2019, all patients who underwent valvular surgery for IE were included in the study. The primary endpoint was early postoperative mortality. A covariate balancing propensity score was developed to minimize the differences between the culture-positive IE (CPIE) and culture-negative IE (CNIE) cohorts. Using the estimated propensity scores as weights, an inverse probability treatment weighting (IPTW) model was built to generate a weighted cohort. Then, to adjust for confounding related to CPIE and CNIE, a doubly robust method that combines regression model with IPTW by propensity score was adopted to estimate the causal effect of the exposure on the outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>During the study period, 327 consecutive patients underwent valvular repair\/replacement with the use of cardiopulmonary bypass and cardioplegic cardiac arrest for IE. Their mean age was 61.4 \u00b1 15.4 years, and 246 were males (75.2%). Native valve IE and prosthetic valve IE accounted for 87.5% and 12.5% of cases, respectively. Aortic (182\/327, 55.7%) and mitral valves (166\/327, 50.8%) were mostly involved; 20.5% of isolated mitral valve diseases were repaired (22\/107 patients). The tricuspid valve was involved in 10 patients (3.3%), and the pulmonary valve in 1 patient (&lt;1%). Fifty-nine patients had multiple-valve disease (18.0%). Blood cultures were negative in 136\/327 (41.6 %). A higher postoperative mortality was registered in CNIE than in CPIE patients (19% vs 9%, respectively, <jats:italic>p<\/jats:italic> = 0.01). The doubly robust analysis after IPTW by propensity score showed CNIE to be associated with early postoperative mortality (odds ratio 2.10; 95% CI, 1.04\u20134.26, <jats:italic>p<\/jats:italic> = 0.04).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In our cohort, CNIE was associated with a higher early postoperative mortality in surgically treated IE patients after dedicated adjustment for confounding. In this perspective, any effort to improve preoperative microbiological diagnosis, thus allowing targeted therapeutic initiatives, might lead to overall better postoperative outcomes in surgically treated IE.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/med-2020-0193","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T07:21:15Z","timestamp":1594020075000},"page":"571-579","source":"Crossref","is-referenced-by-count":17,"title":["Culture-negative infective endocarditis (CNIE): impact on postoperative mortality"],"prefix":"10.1515","volume":"15","author":[{"given":"Antonio","family":"Salsano","sequence":"first","affiliation":[{"name":"Division of Cardiac Surgery, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele Roberto","family":"Giacobbe","sequence":"additional","affiliation":[{"name":"Clinica Malattie Infettive, Ospedale Policlinico San Martino \u2013 IRCCS , Genoa , Italy"},{"name":"Department of Health Sciences (DISSAL), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Del Puente","sequence":"additional","affiliation":[{"name":"Clinica Malattie Infettive, Ospedale Policlinico San Martino \u2013 IRCCS , Genoa , Italy"},{"name":"Department of Health Sciences (DISSAL), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Natali","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ambra","family":"Miette","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Moscatelli","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Internal Medicine (DIMI), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Perocchio","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Scarano","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Internal Medicine (DIMI), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Italo","family":"Porto","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Internal Medicine (DIMI), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Mariscalco","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa , Genova , Italy"},{"name":"Department of Cardiac Surgery, Glenfield Hospital, University Hospitals of Leicester , Leicester , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Bassetti","sequence":"additional","affiliation":[{"name":"Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa , Genova , Italy"},{"name":"Department of Health Sciences (DISSAL), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Santini","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, Ospedale Policlinico San Martino, University of Genoa , Genova , Italy"},{"name":"Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa , Genova , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2020,6,20]]},"reference":[{"key":"2022052423224787422_j_med-2020-0193_ref_001_w2aab3b7d461b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Habib G, Erba PA, Iung B, Donal E, Cosyns B, Laroche C, et al. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study. Eur Heart J. 2019;40:3222\u201332.","DOI":"10.1093\/eurheartj\/ehz620"},{"key":"2022052423224787422_j_med-2020-0193_ref_002_w2aab3b7d461b1b6b1ab2b1b2Aa","doi-asserted-by":"crossref","unstructured":"Zamorano J, Sanz J, Moreno R, Almer\u00eda C, Rodrigo JL, Samedi M, et al. Comparison of outcome in patients with culture-negative versus culture-positive active infective endocarditis. Am J Cardiol. 2001;87:1423\u20135.","DOI":"10.1016\/S0002-9149(01)01570-3"},{"key":"2022052423224787422_j_med-2020-0193_ref_003_w2aab3b7d461b1b6b1ab2b1b3Aa","doi-asserted-by":"crossref","unstructured":"Murashita T, Sugiki H, Kamikubo Y, Yasuda K. Surgical results for active endocarditis with prosthetic valve replacement: impact of culture-negative endocarditis on early and late outcomes. Eur J Cardiothorac Surg. 2004;26:1104\u201311.","DOI":"10.1016\/j.ejcts.2004.08.007"},{"key":"2022052423224787422_j_med-2020-0193_ref_004_w2aab3b7d461b1b6b1ab2b1b4Aa","doi-asserted-by":"crossref","unstructured":"Ferrera C, Vilacosta I, Fern\u00e1ndez C, L\u00f3pez J, Olmos C, Sarri\u00e1 C, et al. Reassessment of blood culture-negative endocarditis: its profile is similar to that of blood culture-positive endocarditis. Rev Esp Cardiol (Engl Ed). 2012;65:891\u2013900.","DOI":"10.1016\/j.rec.2012.04.003"},{"key":"2022052423224787422_j_med-2020-0193_ref_005_w2aab3b7d461b1b6b1ab2b1b5Aa","doi-asserted-by":"crossref","unstructured":"D\u00edez-Villanueva P, Mu\u00f1oz P, Mar\u00edn M, Bermejo J, De Alarc\u00f3n Gonz\u00e1lez A, Fari\u00f1as MC, et al. Infective endocarditis: Absence of microbiological diagnosis is an independent predictor of in hospital mortality. Int J Cardiol. 2016;220:162\u20135.","DOI":"10.1016\/j.ijcard.2016.06.129"},{"key":"2022052423224787422_j_med-2020-0193_ref_006_w2aab3b7d461b1b6b1ab2b1b6Aa","doi-asserted-by":"crossref","unstructured":"Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings, Duke Endocarditis Service. Am J Med. 1994;96:200\u20139.","DOI":"10.1016\/0002-9343(94)90143-0"},{"key":"2022052423224787422_j_med-2020-0193_ref_007_w2aab3b7d461b1b6b1ab2b1b7Aa","doi-asserted-by":"crossref","unstructured":"Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG, Ryan T, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633\u20138.","DOI":"10.1086\/313753"},{"key":"2022052423224787422_j_med-2020-0193_ref_008_w2aab3b7d461b1b6b1ab2b1b8Aa","doi-asserted-by":"crossref","unstructured":"Akins CW, Miller C, Turina MI, Kouchoukos NT, Blackstone EH, Grunkemeier GL, et al. Guidelines for Reporting Mortality and Morbidity After Cardiac Valve Interventions. Ann Thorac Surg. 2008;85:1490\u20135.","DOI":"10.1016\/j.athoracsur.2007.12.082"},{"key":"2022052423224787422_j_med-2020-0193_ref_009_w2aab3b7d461b1b6b1ab2b1b9Aa","doi-asserted-by":"crossref","unstructured":"Nashef SA, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, et al. EuroSCORE II. Eur J Cardiothorac Surg. 2012;41:734\u201344.","DOI":"10.1093\/ejcts\/ezs043"},{"key":"2022052423224787422_j_med-2020-0193_ref_010_w2aab3b7d461b1b6b1ab2b1c10Aa","doi-asserted-by":"crossref","unstructured":"Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36:3075\u2013128.","DOI":"10.1093\/eurheartj\/ehv319"},{"key":"2022052423224787422_j_med-2020-0193_ref_011_w2aab3b7d461b1b6b1ab2b1c11Aa","doi-asserted-by":"crossref","unstructured":"Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM\/ESICM\/ACCP\/ATS\/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29:530\u20138.","DOI":"10.1007\/s00134-003-1662-x"},{"key":"2022052423224787422_j_med-2020-0193_ref_012_w2aab3b7d461b1b6b1ab2b1c12Aa","doi-asserted-by":"crossref","unstructured":"Funk MJ, Westreich D, Wiesen C, St\u00fcrmer T, Brookhart MA, Davidian M. Doubly robust estimation of causal effects. Am J Epidemiol. 2011;173:761\u20137.","DOI":"10.1093\/aje\/kwq439"},{"key":"2022052423224787422_j_med-2020-0193_ref_013_w2aab3b7d461b1b6b1ab2b1c13Aa","doi-asserted-by":"crossref","unstructured":"Imai K, Ratkovic M. Covariate balancing propensity score. J R Stat Soc B. 2014;76:243\u201363.","DOI":"10.1111\/rssb.12027"},{"key":"2022052423224787422_j_med-2020-0193_ref_014_w2aab3b7d461b1b6b1ab2b1c14Aa","doi-asserted-by":"crossref","unstructured":"Cole SR, Hern\u00e1n MA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol. 2008;168:656\u201364.","DOI":"10.1093\/aje\/kwn164"},{"key":"2022052423224787422_j_med-2020-0193_ref_015_w2aab3b7d461b1b6b1ab2b1c15Aa","doi-asserted-by":"crossref","unstructured":"Pencina MJ, D'Agostino Sr RB, D'Agostino Jr RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157\u201372.","DOI":"10.1002\/sim.2929"},{"key":"2022052423224787422_j_med-2020-0193_ref_016_w2aab3b7d461b1b6b1ab2b1c16Aa","doi-asserted-by":"crossref","unstructured":"Wang G, Aban I. Application of inverse probability weights in survival analysis. J Nucl Cardiol. 2015;22:611\u20133.","DOI":"10.1007\/s12350-015-0157-9"},{"key":"2022052423224787422_j_med-2020-0193_ref_017_w2aab3b7d461b1b6b1ab2b1c17Aa","doi-asserted-by":"crossref","unstructured":"Kundu S, Aulchenko YS, van Duijn CM, Janssens AC. PredictABEL: an R package for the assessment of risk prediction models. Eur J Epidemiol. 2011;26:261\u20134.","DOI":"10.1007\/s10654-011-9567-4"},{"key":"2022052423224787422_j_med-2020-0193_ref_018_w2aab3b7d461b1b6b1ab2b1c18Aa","unstructured":"Greifer N Cobalt: covariate balance tables and plots. R package version 3.7.0, 2019, available at: https:\/\/CRAN.R-project.org\/package=cobalt."},{"key":"2022052423224787422_j_med-2020-0193_ref_019_w2aab3b7d461b1b6b1ab2b1c19Aa","doi-asserted-by":"crossref","unstructured":"Salsano A, Giacobbe DR, Sportelli E, Olivieri GM, Natali R, Prevosto M, et al. Aortic cross-clamp time and cardiopulmonary bypass time: prognostic implications in patients operated on for infective endocarditis. Interact Cardiovasc Thorac Surg. 2018;27:328\u201335.","DOI":"10.1093\/icvts\/ivy085"},{"key":"2022052423224787422_j_med-2020-0193_ref_020_w2aab3b7d461b1b6b1ab2b1c20Aa","doi-asserted-by":"crossref","unstructured":"Tattevin P, Watt G, Revest M, Arvieux C, Fournier P-E. Update on blood culture negative endocarditis. Med Mal Infect. 2015;45:1\u20138.","DOI":"10.1016\/j.medmal.2014.11.003"},{"key":"2022052423224787422_j_med-2020-0193_ref_021_w2aab3b7d461b1b6b1ab2b1c21Aa","doi-asserted-by":"crossref","unstructured":"Lepidi H, Durack DT, Raoult D. Diagnostic methods current best practices and guidelines for histologic evaluation in infective endocarditis. Infect Dis Clin N Am. 2002;16:339\u201361.","DOI":"10.1016\/S0891-5520(02)00005-3"},{"key":"2022052423224787422_j_med-2020-0193_ref_022_w2aab3b7d461b1b6b1ab2b1c22Aa","doi-asserted-by":"crossref","unstructured":"Naber CK, Erbel R. Infective endocarditis with negative blood cultures. Int J Antimicrob Agents. 2007;30(Suppl 1):S32\u20136.","DOI":"10.1016\/j.ijantimicag.2007.07.017"},{"key":"2022052423224787422_j_med-2020-0193_ref_023_w2aab3b7d461b1b6b1ab2b1c23Aa","doi-asserted-by":"crossref","unstructured":"Di Mauro M, Actis Dato GM, Barilli F, Gelsomino S, Sant\u00e8 P, Della Corte A, et al. A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE. Int J Cardiol. 2017;241:97\u2013102.","DOI":"10.1016\/j.ijcard.2017.03.148"},{"key":"2022052423224787422_j_med-2020-0193_ref_024_w2aab3b7d461b1b6b1ab2b1c24Aa","doi-asserted-by":"crossref","unstructured":"Selton-Suty C, C\u00e9lard M, Le Moing V, Doco-Lecompte T, Chirouze C, Iung B, et al. Preeminence of Staphylococcus aureus in infective endocarditis: a 1-year population-based survey. Clin Infect Dis. 2012;54:1230\u20139.","DOI":"10.1093\/cid\/cis199"},{"key":"2022052423224787422_j_med-2020-0193_ref_025_w2aab3b7d461b1b6b1ab2b1c25Aa","doi-asserted-by":"crossref","unstructured":"Phua J, Ngerng W, See K, Tay C, Kiong T, Limet H, et al. Characteristics and outcomes of culture negative versus culture-positive severe sepsis. Crit Care. 2013;17:R202.","DOI":"10.1186\/cc12896"},{"key":"2022052423224787422_j_med-2020-0193_ref_026_w2aab3b7d461b1b6b1ab2b1c26Aa","doi-asserted-by":"crossref","unstructured":"Giacinto O, Satriano U, Nenna A, Spadaccio C, Lusini M, Mastroianni C, et al. Inflammatory response and endothelial dysfunction following cardiopulmonary bypass: pathophysiology and pharmacological targets. Recent Pat Inflamm Allergy Drug Discovery. 2019;13:158\u201373.","DOI":"10.2174\/1872213X13666190724112644"},{"key":"2022052423224787422_j_med-2020-0193_ref_027_w2aab3b7d461b1b6b1ab2b1c27Aa","doi-asserted-by":"crossref","unstructured":"De Feo M, Cotrufo M, Carozza A, De Santo LS, Amendolara F, Giordano S, et al. The need for a specific risk prediction system in native valve infective endocarditis surgery. Sci World J. 2012;2012:307571.","DOI":"10.1100\/2012\/307571"},{"key":"2022052423224787422_j_med-2020-0193_ref_028_w2aab3b7d461b1b6b1ab2b1c28Aa","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Sell\u00e9s M, Mu\u00f1oz P, Arn\u00e1iz A, Moreno M, G\u00e1lvez J, Rodr\u00edguez-Roda J, et al. Valve surgery in active infective endocarditis: a simple score to predict in-hospital prognosis. Int J Cardiol. 2014;175:133\u20137.","DOI":"10.1016\/j.ijcard.2014.04.266"},{"key":"2022052423224787422_j_med-2020-0193_ref_029_w2aab3b7d461b1b6b1ab2b1c29Aa","doi-asserted-by":"crossref","unstructured":"Gaca JG, Sheng S, Daneshmand MA, O'Brien S, Rankin JS, Brennan JM, et al. Outcomes for endocarditis surgery in North America: a simplified risk scoring system. J Thorac Cardiovasc Surg. 2011;141:98\u2013106.","DOI":"10.1016\/j.jtcvs.2010.09.016"},{"key":"2022052423224787422_j_med-2020-0193_ref_030_w2aab3b7d461b1b6b1ab2b1c30Aa","doi-asserted-by":"crossref","unstructured":"Costa MA, Wollmann DR, Campos AC, Cunha CL, Carvalho RG, Andrade DF, et al. Risk index for death by infective endocarditis: a multivariate logistic model. Rev Bras Cir Cardiovasc. 2007;22:192\u2013200.","DOI":"10.1590\/S0102-76382007000200007"}],"container-title":["Open Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/view\/journals\/med\/15\/1\/article-p571.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2020-0193\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2020-0193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T23:31:17Z","timestamp":1653435077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2020-0193\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,9,30]]},"published-print":{"date-parts":[[2020,9,30]]}},"alternative-id":["10.1515\/med-2020-0193"],"URL":"https:\/\/doi.org\/10.1515\/med-2020-0193","relation":{},"ISSN":["2391-5463"],"issn-type":[{"value":"2391-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,1]]}}}